rs10496948

Variant names:

• chr2-143353884-C-T
• rs10496948
• NM_018460.4:c.475-81717C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018460.4(ARHGAP15):​c.475-81717C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 152,138 control chromosomes in the GnomAD database, including 415 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.063 (415 hom., cov: 33)
• Consequence: ARHGAP15 NM_018460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 7 publications found

Genes affected

ARHGAP15 (HGNC:21030): (Rho GTPase activating protein 15) RHO GTPases (see ARHA; MIM 165390) regulate diverse biologic processes, and their activity is regulated by RHO GTPase-activating proteins (GAPs), such as ARHGAP15 (Seoh et al., 2003 [PubMed 12650940]).[supplied by OMIM, Mar 2008]

ENSG00000228655 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP15	NM_018460.4	c.475-81717C>T		intron_variant	Intron 6 of 13	ENST00000295095.11	NP_060930.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP15	ENST00000295095.11	c.475-81717C>T		intron_variant	Intron 6 of 13	1	NM_018460.4	ENSP00000295095.6

Frequencies

GnomAD3 genomes AF: 0.0627 AC: 9530 AN: 152020 Hom.: 416 Cov.: 33

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.0542

Gnomad ASJ AF: 0.0616

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.0954

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0945

Gnomad OTH AF: 0.0638

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0626 AC: 9531 AN: 152138 Hom.: 415 Cov.: 33 AF XY: 0.0617 AC XY: 4589 AN XY: 74366

African (AFR) AF: 0.0162 AC: 674 AN: 41516

American (AMR) AF: 0.0541 AC: 826 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0616 AC: 214 AN: 3472

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.0203 AC: 98 AN: 4826

European-Finnish (FIN) AF: 0.0954 AC: 1006 AN: 10544

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0945 AC: 6426 AN: 68008

Other (OTH) AF: 0.0631 AC: 133 AN: 2108

Alfa AF: 0.0775 Hom.: 882

Bravo AF: 0.0564

Asia WGS AF: 0.00809 AC: 28 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.76
DANN	Benign	0.55
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10496948; hg19: chr2-144111453; COSMIC: COSV54520326;